Future studies will be directed at attempting to delineate differences in cholesterol metabolism between normal cultured cells and those derived from patients with the various hyperlipoproteinemias. The differential effects of serum, plasma, and various fractions of lipoproteins on the activity of HMG CoA reductase will be evaluated in these cell lines. In addition, detailed studies of HMG CoA reductase activity in the various hybrids will be conducted in an attempt to determine the nature, and possibly the chromosomal location, of those factors that are responsible for the normal feedback inhibition exerted by cholesterol on HMG CoA reductase. Similar studies will be employed to differentiate more clearly between homozygous type II hyperlipoproteinemia and type III hyperlipoproteinemia.